Protease‐activated receptor‐1 drives pancreatic cancer progression and chemoresistance. Issue 10 (19th June 2014)

• Record Type: Journal Article
• Authors: Queiroz, Karla C.S.; Shi, Kun; Duitman, JanWillem; Aberson, Hella L.; Wilmink, Johanna W.; van Noesel, Carel J.M.; Richel, Dick J.; Spek, C. Arnold
• Is Part Of: International journal of cancer. Volume 135:Issue 10(2014:Nov. 15)
• Page Start: 2294
• Page End: 2304
• Publication Date: 2014-06-19
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28726
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Protease activated receptor (PAR)‐1 expression in tumor cells is associated with disease progression and overall survival in a variety of cancers of epithelial origin; however, the importance of PAR‐1 in the tumor microenvironment remains unexplored. Utilizing an orthotopic pancreatic cancer model in which tumor cells are PAR‐1 positive whereas stromal cells are PAR‐1 negative, we show that PAR‐1 expression in the microenvironment drives progression and induces chemoresistance of pancreatic cancer. PAR‐1 enhances monocyte recruitment into the tumor microenvironment by regulating monocyte migration and fibroblast dependent chemokine production thereby inducing chemoresistance. Overall, our data identify a novel role of PAR‐1 in the pancreatic tumor microenvironment and suggest that PAR‐1 may be an attractive target to reduce drug resistance in pancreatic cancer.</p> </abstract>